1. Field of the Invention
The present invention relates to the use of surface modified biocompatible materials to promote the attachment of bone or bone-like cells to an implant surface. The surface of the biomaterials, which may include hydrogels, when modified in accordance with the description herein, directs the cells that migrate to the implant site to differentiate into cells that attach and lay down bone or bone-derivative material, or cartilage or cartilaginous material further enhancing the biocompatibility of the implanted device.
2. Background Art
Materials used in the construction of implantable medical devices must be nontoxic, nonantigenic, and noninflammatory. Hydrogels are a preferred type of polymeric material for implantable devices. Because of their high water content, analogous to living tissue, they are superior in biocompatibility to non-hydrous polymeric materials.
U.S. Pat. No. 5,981,826, issued to Ku et al., describes the preparation of polyvinyl alcohol hydrogels (PVA-H) by physically crosslinking an aqueous solution of polyvinyl alcohol (PVA) to produce a gel. The crosslinking is accomplished by subjecting the aqueous PVA solution to multiple cycles of freezing and thawing. One limitation of the prior art is that the hydrogels produced are relatively nonporous and the pore size and degree of porosity, that is the density of the pores within the hydrogel, cannot vary independently of the mechanical properties or stiffness of the hydrogel.
Methods for producing certain porous hydrogels also exist in the art. U.S. Pat. No. 6,268,405 issued to Yao et al., describes methods for creating porous PVA-Hs by including immiscible materials in the polymerization process. After the hydrogel is polymerized, the included immiscible materials are washed out of the hydrogel by an appropriate solvent, yielding pores which are broadly distributed throughout the hydrogel. Controlling the size and density of the pores is accomplished by varying the molecular weight of the immiscible materials. A disadvantage of Yao et al. is that the range of attainable pore sizes is limited. Moreover, the invention of Yao et al. is limited in that it can only produce hydrogels whose pores extend throughout the hydrogel. The pores in Yao et al. are intended to create vascularization of the hydrogel in soft or non-load bearing tissue. A further disadvantage of Yao et al. is that the pore sizes are broadly distributed about the average pore size.
In addition to crosslinking by physical means, hydrogels may be chemically crosslinked using, for example, methods similar to those described by Müller in U.S. Pat. No. 5,789,464. Similarly, chemical crosslinking or polymerization methods may also be used to adhere hydrogels to surfaces, including biological tissues. U.S. Pat. No. 5,900,245, issued to Sawhney et al., describes applications of these techniques. These and other methods for the crosslinking or further polymerization of hydrogels are derived from methods used in the polymer industry and are well known in the art.
Artificial discs intended for the replacement of a damaged intravertebral disc have been described. These are typically articulated devices comprising two rigid metal plates adhered to opposite ends of an elastomeric core. In use, the artificial disc is placed in the intervertebral space and the metal plates are secured to the surfaces of adjacent vertebrae. Various embodiments of artificial discs of this type are described in U.S. Pat. Nos. 5,674,296 and 6,156,067, issued to Bryan et al., U.S. Pat. No. 5,824,094, issued to Serhan et al., U.S. Pat. No. 6,402,785, issued to Zdeblick et al. More recent embodiments, e.g. U.S. Pat. No. 6,419,704, issued to Ferree and U.S. Pat. No. 6,482,234, issued to Weber et al., include descriptions of elastomeric cores that may be formed from materials with different elasticities to better mimic the native structure of spinal discs.
The disadvantages of the artificial disc devices of the prior art are numerous. These prior art devices require the mechanical attachment of rigid artificial materials, such as titanium, directly to the bone with screws, staples, nails, cement, or other mechanical means. These rigid materials are only minimally compatible with natural, living bone and separation of the implant from the bone is often observed over long-term implantation. In addition, materials used in artificial discs of the prior art have physical and mechanical properties distinctly different from those of natural spinal, discs and thus, inadequately duplicate the desired properties of native spinal discs.
Vertebral fusion is still the most commonly performed procedure to treat debilitating pain associated with degenerative spinal disc disease or disc trauma, despite the fact that the procedure has many drawbacks. Vertebral fusion increases stress and strain on the discs adjacent to the fusion site, and it is now widely accepted that fusion is responsible for the accelerated degeneration of adjacent levels. Current multicomponent spinal disc prosthesis designs, elastomeric cores with metal plates on both the upper and lower surfaces, are susceptible to problems with interfacial bonding and wear. These designs have shown spontaneous device detachment due to retraction of bone tissue from the metal surface.
Bone ingrowth and attachment in the art has often required the use of bone promoting growth factors. For example, U.S. Pat. No. 5,108,436, issued to Chu et al., describes using a porous implant for use in load bearing bone replacement which is used in combination with an osteogenic factor such as TGF-β.
Biomedical devices which are implanted in or around bone often fail because of fibrinogen encapsulation of the implant instead of cellular attachment to the implant itself. This encapsulation is a defensive reaction attempting to minimize contact between the body and the implant and is considered a sign of implant incompatibility.
Moreover, the art of bone ingrowth to implantable surface contains a multitude of examples relating to porous directed ingrowth where bone essentially grows into and around channels of the implant. For example, U.S. Pat. No. 4,911,720, issued to Collier et al., discusses the ingrowth of bone into interconnecting pores which essentially locks bone into place. This method is disadvantageous in that bone does not actually attach to the material, instead bone attaches to other bone around the implant. In the unfortunate event that an implant must be removed, this type of Collier ingrowth results in large amounts of disruption to the surrounding bone tissue.
The present invention describes a biomaterial for implantation into the body. The biomaterial, which can be a hydrogel, possesses a textured surface which is comprised of superficial surface pores. As used herein, the term pores shall include cavities, indentations, holes and openings. Stated differently, the pores on the surface of the hydrogel substrate do not extend throughout the hydrogel but instead remain within a region near the surface. The hydrogel substrate can be comprised of two or more pore sizes. Specifically, the pores of the first size each have a diameter of between 3 and 1000 micrometers, preferably between 10 and 300 micrometers, and preferably between 30 and 100 micrometers. Further, the pores of the second size would each have a diameter of between 0.5 to 20 micrometers, preferably between 1 to 10 micrometers, and preferably between 2 and 5 micrometers. One embodiment of the present invention provides the second, smaller pores disposed within the first, larger pores. The superficial pores of the present invention extend into the hydrogel substrate less than 1 millimeter, preferably 500 micrometers, and preferably 200 micrometers, from the surface. The hydrogel substrate of the present embodiment can comprise polyvinyl alcohol having a water content of at least 5% and preferably at least 30%.
The present invention is also drawn to a hydrogel substrate comprising a hydrogel surface having thereon a plurality of first substantially uniform superficial pores and a unique plurality of second substantially uniform superficial pores. This hydrogel can possess two different yet substantially uniform superficial pore sizes grouped into a first, larger pore size and a second, smaller pore size. The pores of one size are substantially uniform in diameter relative to the other pores of the same size. Specifically, the first pores have an average diameter of between 2 and 600 micrometers, preferably between 5 and 200 micrometers, and preferably between 20 and 60 micrometers. Further, the second pores have an average diameter of between 0.1 and 10 micrometers, preferably between 0.2 to 5 micrometers, and preferably between 0.5 to 2 micrometers. The superficial pores of the present invention can be arranged so that the smaller, second pores are within the larger, first pores. The superficial pores of the present invention extend into the hydrogel substrate less than 1 millimeter, preferably no more than 500 micrometers, and preferably no more than 200 micrometers. The hydrogel substrate of the present embodiment can be made up of polyvinyl alcohol having a water content of at least 5% and preferably at least 30% w/w of the overall hydrogel.